Glucose-6-P/phosphate translocator2 mediates the phosphoglucose-isomerase1-independent response to microbial volatiles.

In Arabidopsis (Arabidopsis thaliana), the plastidial isoform of phosphoglucose isomerase (PGI1) mediates photosynthesis, metabolism, and development, probably due to its involvement in the synthesis of isoprenoid-derived signals in vascular tissues. Microbial volatile compounds (VCs) with molecular masses of <45 Da promote photosynthesis, growth, and starch overaccumulation in leaves through PGI1-independent mechanisms. Exposure to these compounds in leaves enhances the levels of GLUCOSE-6-PHOSPHATE/PHOSPHATE TRANSLOCATOR2 (GPT2) transcripts. We hypothesized that the PGI1-independent response to microbial volatile emissions involves GPT2 action. To test this hypothesis, we characterized the responses of wild-type (WT), GPT2-null gpt2-1, PGI1-null pgi1-2, and pgi1-2gpt2-1 plants to small fungal VCs. In addition, we characterized the responses of pgi1-2gpt2-1 plants expressing GPT2 under the control of a vascular tissue- and root tip-specific promoter to small fungal VCs. Fungal VCs promoted increases in growth, starch content, and photosynthesis in WT and gpt2-1 plants. These changes were substantially weaker in VC-exposed pgi1-2gpt2-1 plants but reverted to WT levels with vascular and root tip-specific GPT2 expression. Proteomic analyses did not detect enhanced levels of GPT2 protein in VC-exposed leaves and showed that knocking out GPT2 reduced the expression of photosynthesis-related proteins in pgi1-2 plants. Histochemical analyses of GUS activity in plants expressing GPT2-GUS under the control of the GPT2 promoter showed that GPT2 is mainly expressed in root tips and vascular tissues around hydathodes. Overall, the data indicated that the PGI1-independent response to microbial VCs involves resetting of the photosynthesis-related proteome in leaves through long-distance GPT2 action.

Action mechanisms of small microbial volatile compounds in plants.

Microorganisms communicate with plants by exchanging chemical signals throughout the phytosphere. Before direct contact with plants occurs, beneficial microorganisms emit a plethora of volatile compounds that promote plant growth and photosynthesis as well as developmental, metabolic, transcriptional, and proteomic changes in plants. These compounds can also induce systemic drought tolerance and improve water and nutrient acquisition. Recent studies have shown that this capacity is not restricted to beneficial microbes; it also extends to phytopathogens. Plant responses to microbial volatile compounds have frequently been associated with volatile organic compounds with molecular masses ranging between ~ 45Da and 300Da. However, microorganisms also release a limited number of volatile compounds with molecular masses of less than ~45Da that react with proteins and/or act as signaling molecules. Some of these compounds promote photosynthesis and growth when exogenously applied in low concentrations. Recently, evidence has shown that small volatile compounds are important determinants of plant responses to microbial volatile emissions. However, the regulatory mechanisms involved in these responses remain poorly understood. This review summarizes current knowledge of biochemical and molecular mechanisms involved in plant growth, development, and metabolic responses to small microbial volatile compounds.

Stroke Acute Management and Outcomes During the COVID-19 Outbreak: A Cohort Study From the Madrid Stroke Network.

BACKGROUND AND PURPOSE: The coronavirus disease 2019 (COVID-19) outbreak has added challenges to providing quality acute stroke care due to the reallocation of stroke resources to COVID-19. Case series suggest that patients with COVID-19 have more severe strokes; however, no large series have compared stroke outcomes with contemporary non-COVID-19 patients. Purpose was to analyze the impact of COVID-19 pandemic in stroke care and to evaluate stroke outcomes according to the diagnosis of COVID-19. METHODS: Retrospective multicenter cohort study including consecutive acute stroke patients admitted to 7 stroke centers from February 25 to April 25, 2020 (first 2 months of the COVID-19 outbreak in Madrid). The quality of stroke care was measured by the number of admissions, recanalization treatments, and time metrics. The primary outcome was death or dependence at discharge. RESULTS: A total of 550 acute stroke patients were admitted. A significant reduction in the number of admissions and secondary interhospital transfers was found. COVID-19 was confirmed in 105 (19.1%) patients, and a further 19 patients were managed as suspected COVID-19 (3.5%). No differences were found in the rates of reperfusion therapies in ischemic strokes (45.5% non-COVID-19, 35.7% confirmed COVID-19, and 40% suspected COVID-19; P=0.265). However, the COVID-19 group had longer median door-to-puncture time (110 versus 80 minutes), which was associated with the performance of chest computed tomography. Multivariate analysis confirmed poorer outcomes for confirmed or suspected COVID-19 (adjusted odds ratios, 2.05 [95% CI, 1.12-3.76] and 3.56 [95% CI, 1.15-11.05], respectively). CONCLUSIONS: This study confirms that patients with COVID-19 have more severe strokes and poorer outcomes despite similar acute management. A well-established stroke care network helps to diminish the impact of such an outbreak in stroke care, reducing secondary transfers and allowing maintenance of reperfusion therapies, with a minor impact on door-to-puncture times, which were longer in patients who underwent chest computed tomography.

Plastidial Phosphoglucose Isomerase Is an Important Determinant of Seed Yield through Its Involvement in Gibberellin-Mediated Reproductive Development and Storage Reserve Biosynthesis in Arabidopsis.

The plastid-localized phosphoglucose isomerase isoform PGI1 is an important determinant of growth in Arabidopsis thaliana, likely due to its involvement in the biosynthesis of plastidial isoprenoid-derived hormones. Here, we investigated whether PGI1 also influences seed yields. PGI1 is strongly expressed in maturing seed embryos and vascular tissues. PGI1-null pgi1-2 plants had ∼60% lower seed yields than wild-type plants, with reduced numbers of inflorescences and thus fewer siliques and seeds per plant. These traits were associated with low bioactive gibberellin (GA) contents. Accordingly, wild-type phenotypes were restored by exogenous GA application. pgi1-2 seeds were lighter and accumulated ∼50% less fatty acids (FAs) and ∼35% less protein than wild-type seeds. Seeds of cytokinin-deficient plants overexpressing CYTOKININ OXIDASE/DEHYDROGENASE1 (35S:AtCKX1) and GA-deficient ga20ox1 ga20ox2 mutants did not accumulate low levels of FAs, and exogenous application of the cytokinin 6-benzylaminopurine and GAs did not rescue the reduced weight and FA content of pgi1-2 seeds. Seeds from reciprocal crosses between pgi1-2 and wild-type plants accumulated wild-type levels of FAs and proteins. Therefore, PGI1 is an important determinant of Arabidopsis seed yield due to its involvement in two processes: GA-mediated reproductive development and the metabolic conversion of plastidial glucose-6-phosphate to storage reserves in the embryo.

Neurological complications of COVID-19 in hospitalized patients: The registry of a neurology department in the first wave of the pandemic.

OBJECTIVE: To describe the spectrum of neurological complications observed in a hospital-based cohort of COVID-19 patients who required a neurological assessment. METHODS: We conducted an observational, monocentric, prospective study of patients with a COVID-19 diagnosis hospitalized during the 3-month period of the first wave of the COVID-19 pandemic in a tertiary hospital in Madrid (Spain). We describe the neurological diagnoses that arose after the onset of COVID-19 symptoms. These diagnoses could be divided into different groups. RESULTS: Only 71 (2.6%) of 2750 hospitalized patients suffered at least one neurological complication (77 different neurological diagnoses in total) during the timeframe of the study. The most common diagnoses were neuromuscular disorders (33.7%), cerebrovascular diseases (CVDs) (27.3%), acute encephalopathy (19.4%), seizures (7.8%), and miscellanea (11.6%) comprising hiccups, myoclonic tremor, Horner syndrome and transverse myelitis. CVDs and encephalopathy were common in the early phase of the COVID-19 pandemic compared to neuromuscular disorders, which usually appeared later on (p = 0.005). Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction was negative in 15/15 samples. The mortality was higher in the CVD group (38.1% vs. 8.9%; p = 0.05). CONCLUSIONS: The prevalence of neurological complications is low in patients hospitalized for COVID-19. Different mechanisms appear to be involved in these complications, and there was no evidence of direct invasion of the nervous system in our cohort. Some of the neurological complications can be classified into early and late neurological complications of COVID-19, as they occurred at different times following the onset of COVID-19 symptoms.

Fewer COVID-19-associated strokes and reduced severity during the second COVID-19 wave: The Madrid Stroke Network.

BACKGROUND AND PURPOSE: The experience gained during the first COVID-19 wave could have mitigated the negative impact on stroke care in the following waves. Our aims were to analyze the characteristics and outcomes of patients with stroke admitted during the second COVID-19 wave and to evaluate the differences in the stroke care provision compared with the first wave. METHODS: This retrospective multicenter cohort study included consecutive stroke patients admitted to any of the seven hospitals with stroke units (SUs) and endovascular treatment facilities in the Madrid Health Region. The characteristics of the stroke patients with or without a COVID-19 diagnosis were compared and the organizational changes in stroke care between the first wave (25 February to 25 April 2020) and second wave (21 July to 21 November 2020) were analyzed. RESULTS: A total of 550 and 1191 stroke patients were admitted during the first and second COVID-19 waves, respectively, with an average daily admission rate of nine patients in both waves. During the second wave, there was a decrease in stroke severity (median National Institutes of Health Stroke Scale 5 vs. 6; p = 0.000), in-hospital strokes (3% vs. 8.1%) and in-hospital mortality (9.9% vs. 15.9%). Furthermore, fewer patients experienced concurrent COVID-19 (6.8% vs. 19.1%), and they presented milder COVID-19 and less severe strokes. Fewer hospitals reported a reduction in the number of SU beds or deployment of SU personnel to COVID-19 dedicated wards during the second wave. CONCLUSIONS: During the second COVID-19 wave, fewer stroke patients were diagnosed with COVID-19, and they had less stroke severity and milder COVID-19.

Acute Stroke Care during the COVID-19 Pandemic: Reduction in the Number of Admissions of Elderly Patients and Increase in Prehospital Delays.

INTRODUCTION: We analyzed whether the coronavirus disease 2019 (COVID-19) crisis affected acute stroke care in our center during the first 2 months of lockdown in Spain. METHODS: This is a single-center, retrospective study. We collected demographic, clinical, and radiological data; time course; and treatment of patients meeting the stroke unit admission criteria from March 14 to May 14, 2020 (COVID-19 period group). Data were compared with the same period in 2019 (pre-COVID-19 period group). RESULTS: 195 patients were analyzed; 83 in the COVID-19 period group, resulting in a 26% decline of acute strokes and transient ischemic attacks (TIAs) admitted to our center compared with the previous year (p = 0.038). Ten patients (12%) tested positive for PCR SARS-CoV-2. The proportion of patients aged 65 years and over was lower in the COVID-19 period group (53 vs. 68.8%, p = 0.025). During the pandemic period, analyzed patients were more frequently smokers (27.7 vs. 10.7%, p = 0.002) and had less frequently history of prior stroke (13.3 vs. 25%, p = 0.043) or atrial fibrillation (9.6 vs. 25%, p = 0.006). ASPECTS score was lower (9 [7-10] vs. 10 [8-10], p = 0.032), NIHSS score was slightly higher (5 [2-14] vs. 4 [2-8], p = 0.122), onset-to-door time was higher (304 [93-760] vs. 197 [91.25-645] min, p = 0.104), and a lower proportion arrived within 4.5 h from onset of symptoms (43.4 vs. 58%, p = 0.043) during the CO-VID-19 period. There were no differences between proportion of patients receiving recanalization treatment (intravenous thrombolysis and/or mechanical thrombectomy) and in-hospital delays. CONCLUSION: We observed a reduction in the number of acute strokes and TIAs admitted during the COVID-19 period. This drop affected especially elderly patients, and despite a delay in their arrival to the emergency department, the proportion of patients treated with recanalization therapies was preserved.

Feasibility of multidisciplinary telehealth evaluations in atypical dementia.

INTRODUCTION: While cognitive assessment by videoconference has become possible over the past decade, the COVID-19 pandemic underscores the critical need for expansion and examination of these methods, their appropriateness for various patient populations, and their benefits and limitations. Validity and reliability studies of tele-neuropsychological testing have been conducted in MCI or mild AD dementia patients (e.g., MMSE=25+); few studies have assessed the feasibility of neurologic examination by video, and none in atypical dementias, assuming that patients with some types (e.g., language, comportment) or greater severity of cognitive-behavioral impairment would be unable to participate. Here we report the feasibility of telehealth services for a multi-disciplinary dementia subspecialty clinic that include cognitive-behavioral and neurologic assessment with patients with atypical neurodegenerative syndromes. METHODS: 104 patient-carepartner (P-C) dyads met with providers in the MGH FTD Unit by videoconference (March-December, 2020) for routine clinical care. P-Cs completed validated questionnaires assessing cognition-mood/behavior/function on REDCap prior to video clinical interview and cognitive assessment, including the MoCA and Boston Cognitive Exam (BCE2.0), a newly revised brief cognitive assessment battery adapted for telehealth. P-Cs met with a neurologist for a basic neurologic examination (including eye-movement examination), review of assessment results, and discussion of care plan. P-Cs completed a satisfaction survey. RESULTS: The 104 P-Cs included a range of atypical neurodegenerative disorders (bvFTD, PCA, PPA, CBS, PSP, eoAD, Multidomain syndrome) mild-to-severe impairment (CDR range: 0-3). 76% completed the MoCA (25% had CDR=2). 36% also completed the BCEv2. Comparison of remote assessment data to previous in-person testing is ongoing. Of P-Cs who completed a satisfaction survey, all reported being "very satisfied" with the appointment, with 93% open to participating in a remote visit again. 87% found the telehealth visit comparable to an in-person visit. 66% preferred a future combination of remote and in-person visits. CONCLUSIONS: Multi-disciplinary telehealth visits appear to be feasible with patients with atypical cognitive-behavioral syndromes of across the severity spectrum. P-Cs report a high degree of satisfaction with the telehealth visit and an openness to ongoing telehealth visits. Results have implications for increasing accessibility of multidisciplinary medical services for patients and families living with complex forms of dementia.

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Volatiles from the fungal phytopathogen Penicillium aurantiogriseum modulate root metabolism and architecture through proteome resetting.

Volatile compounds (VCs) emitted by the fungal phytopathogen Penicillium aurantiogriseum promote root growth and developmental changes in Arabidopsis. Here we characterised the metabolic and molecular responses of roots to fungal volatiles. Proteomic analyses revealed that these compounds reduce the levels of aquaporins, the iron carrier IRT1 and apoplastic peroxidases. Fungal VCs also increased the levels of enzymes involved in the production of mevalonate (MVA)-derived isoprenoids, nitrogen assimilation and conversion of methionine to ethylene and cyanide. Consistently, fungal VC-treated roots accumulated high levels of hydrogen peroxide (H2 O2 ), MVA-derived cytokinins, ethylene, cyanide and long-distance nitrogen transport amino acids. qRT-PCR analyses showed that many proteins differentially expressed by fungal VCs are encoded by VC non-responsive genes. Expression patterns of hormone reporters and developmental characterisation of mutants provided evidence for the involvement of cyanide scavenging and enhanced auxin, ethylene, cytokinin and H2 O2 signalling in the root architecture changes promoted by fungal VCs. Our findings show that VCs from P. aurantiogriseum modify root metabolism and architecture, and improve nutrient and water use efficiencies through transcriptionally and non-transcriptionally regulated proteome resetting mechanisms. Some of these mechanisms are subject to long-distance regulation by photosynthesis and differ from those triggered by VCs emitted by beneficial microorganisms.

The Energy-Signaling Hub SnRK1 Is Important for Sucrose-Induced Hypocotyl Elongation.

Emerging seedlings respond to environmental conditions such as light and temperature to optimize their establishment. Seedlings grow initially through elongation of the hypocotyl, which is regulated by signaling pathways that integrate environmental information to regulate seedling development. The hypocotyls of Arabidopsis (Arabidopsis thaliana) also elongate in response to sucrose. Here, we investigated the role of cellular sugar-sensing mechanisms in the elongation of hypocotyls in response to Suc. We focused upon the role of SnRK1, which is a sugar-signaling hub that regulates metabolism and transcription in response to cellular energy status. We also investigated the role of TPS1, which synthesizes the signaling sugar trehalose-6-P that is proposed to regulate SnRK1 activity. Under light/dark cycles, we found that Suc-induced hypocotyl elongation did not occur in tps1 mutants and overexpressors of KIN10 (AKIN10/SnRK1.1), a catalytic subunit of SnRK1. We demonstrate that the magnitude of Suc-induced hypocotyl elongation depends on the day length and light intensity. We identified roles for auxin and gibberellin signaling in Suc-induced hypocotyl elongation under short photoperiods. We found that Suc-induced hypocotyl elongation under light/dark cycles does not involve another proposed sugar sensor, HEXOKINASE1, or the circadian oscillator. Our study identifies novel roles for KIN10 and TPS1 in mediating a signal that underlies Suc-induced hypocotyl elongation in light/dark cycles.

Volatile compounds other than CO2 emitted by different microorganisms promote distinct posttranscriptionally regulated responses in plants.

A "box-in-box" cocultivation system was used to investigate plant responses to microbial volatile compounds (VCs) and to evaluate the contributions of organic and inorganic VCs (VOCs and VICs, respectively) to these responses. Arabidopsis plants were exposed to VCs emitted by adjacent Alternaria alternata and Penicillium aurantiogriseum cultures, with and without charcoal filtration. No VOCs were detected in the headspace of growth chambers containing fungal cultures with charcoal filters. However, these growth chambers exhibited elevated CO2 and bioactive CO and NO headspace concentrations. Independently of charcoal filtration, VCs from both fungal phytopathogens promoted growth and distinct developmental changes. Plants cultured at CO2 levels observed in growth boxes containing fungal cultures were identical to those cultured at ambient CO2 . Plants exposed to charcoal-filtered fungal VCs, nonfiltered VCs, or superelevated CO2 levels exhibited transcriptional changes resembling those induced by increased irradiance. Thus, in the "box-in-box" system, (a) fungal VICs other than CO2 and/or VOCs not detected by our analytical systems strongly influence the plants' responses to fungal VCs, (b) different microorganisms release VCs with distinct action potentials, (c) transcriptional changes in VC-exposed plants are mainly due to enhanced photosynthesis signaling, and (d) regulation of some plant responses to fungal VCs is primarily posttranscriptional.

Plant responses to fungal volatiles involve global posttranslational thiol redox proteome changes that affect photosynthesis.

Microorganisms produce volatile compounds (VCs) that promote plant growth and photosynthesis through complex mechanisms involving cytokinin (CK) and abscisic acid (ABA). We hypothesized that plants' responses to microbial VCs involve posttranslational modifications of the thiol redox proteome through action of plastidial NADPH-dependent thioredoxin reductase C (NTRC), which regulates chloroplast redox status via its functional relationship with 2-Cys peroxiredoxins. To test this hypothesis, we analysed developmental, metabolic, hormonal, genetic, and redox proteomic responses of wild-type (WT) plants and a NTRC knockout mutant (ntrc) to VCs emitted by the phytopathogen Alternaria alternata. Fungal VC-promoted growth, changes in root architecture, shifts in expression of VC-responsive CK- and ABA-regulated genes, and increases in photosynthetic capacity were substantially weaker in ntrc plants than in WT plants. As in WT plants, fungal VCs strongly promoted growth, chlorophyll accumulation, and photosynthesis in ntrc-Δ2cp plants with reduced 2-Cys peroxiredoxin expression. OxiTRAQ-based quantitative and site-specific redox proteomic analyses revealed that VCs promote global reduction of the thiol redox proteome (especially of photosynthesis-related proteins) of WT leaves but its oxidation in ntrc leaves. Our findings show that NTRC is an important mediator of plant responses to microbial VCs through mechanisms involving global thiol redox proteome changes that affect photosynthesis.

An Example of Polynomial Expansion: The Reaction of 3(5)-Methyl-1H-Pyrazole with Chloroform and Characterization of the Four Isomers.

The reaction in phase-transfer catalyzed conditions of 3(5)-methyl-1H-pyrazole with chloroform affords four isomers 333, 335, 355 and 555 in proportions corresponding to the polynomial expansion (a + b)³, with a = 0.6 and b = 0.4, a and b being 3-methyl and 5-methyl proportions. The up (u) and down (d) conformation of the pyrazolyl rings with regard to the Csp³â»H atom was established by X-ray crystallography and by ¹H-, 13C- and 15N-NMR in solution combined with gauge-including atomic orbitals (GIAO)/B3LYP/6-311++G(d,p) calculations. A comparison with other X-ray structures of tris-pyrazolylmethanes was carried out.

Arabidopsis Responds to Alternaria alternata Volatiles by Triggering Plastid Phosphoglucose Isomerase-Independent Mechanisms.

Volatile compounds (VCs) emitted by phylogenetically diverse microorganisms (including plant pathogens and microbes that do not normally interact mutualistically with plants) promote photosynthesis, growth, and the accumulation of high levels of starch in leaves through cytokinin (CK)-regulated processes. In Arabidopsis (Arabidopsis thaliana) plants not exposed to VCs, plastidic phosphoglucose isomerase (pPGI) acts as an important determinant of photosynthesis and growth, likely as a consequence of its involvement in the synthesis of plastidic CKs in roots. Moreover, this enzyme plays an important role in connecting the Calvin-Benson cycle with the starch biosynthetic pathway in leaves. To elucidate the mechanisms involved in the responses of plants to microbial VCs and to investigate the extent of pPGI involvement, we characterized pPGI-null pgi1-2 Arabidopsis plants cultured in the presence or absence of VCs emitted by Alternaria alternata We found that volatile emissions from this fungal phytopathogen promote growth, photosynthesis, and the accumulation of plastidic CKs in pgi1-2 leaves. Notably, the mesophyll cells of pgi1-2 leaves accumulated exceptionally high levels of starch following VC exposure. Proteomic analyses revealed that VCs promote global changes in the expression of proteins involved in photosynthesis, starch metabolism, and growth that can account for the observed responses in pgi1-2 plants. The overall data show that Arabidopsis plants can respond to VCs emitted by phytopathogenic microorganisms by triggering pPGI-independent mechanisms.

Volatile compounds emitted by diverse phytopathogenic microorganisms promote plant growth and flowering through cytokinin action.

It is known that volatile emissions from some beneficial rhizosphere microorganisms promote plant growth. Here we show that volatile compounds (VCs) emitted by phylogenetically diverse rhizosphere and non-rhizhosphere bacteria and fungi (including plant pathogens and microbes that do not normally interact mutualistically with plants) promote growth and flowering of various plant species, including crops. In Arabidopsis plants exposed to VCs emitted by the phytopathogen Alternaria alternata, changes included enhancement of photosynthesis and accumulation of high levels of cytokinins (CKs) and sugars. Evidence obtained using transgenic Arabidopsis plants with altered CK status show that CKs play essential roles in this phenomenon, because growth and flowering responses to the VCs were reduced in mutants with CK-deficiency (35S:AtCKX1) or low receptor sensitivity (ahk2/3). Further, we demonstrate that the plant responses to fungal VCs are light-dependent. Transcriptomic analyses of Arabidopsis leaves exposed to A. alternata VCs revealed changes in the expression of light- and CK-responsive genes involved in photosynthesis, growth and flowering. Notably, many genes differentially expressed in plants treated with fungal VCs were also differentially expressed in plants exposed to VCs emitted by the plant growth promoting rhizobacterium Bacillus subtilis GB03, suggesting that plants react to microbial VCs through highly conserved regulatory mechanisms.

Acute toxicities of unrelated bone marrow versus peripheral blood stem cell donation: results of a prospective trial from the National Marrow Donor Program.

Although peripheral blood stem cells (PBSCs) have replaced bone marrow (BM) as the most common unrelated donor progenitor cell product collected, a direct comparison of concurrent PBSC versus BM donation experiences has not been performed. We report a prospective study of 2726 BM and 6768 PBSC donors who underwent collection from 2004 to 2009. Pain and toxicities were assessed at baseline, during G-CSF administration, on the day of collection, within 48 hours of donation, and weekly until full recovery. Peak levels of pain and toxicities did not differ between the 2 donation processes for most donors. Among obese donors, PBSC donors were at increased risk of grade 2 to 4 pain as well as grade 2 to 4 toxicities during the pericollection period. In contrast, BM donors were more likely to experience grade 2 to 4 toxicities at 1 week and pain at 1 week and 1 month after the procedure. BM donors experienced slower recovery, with 3% still not fully recovered at 24 weeks, whereas 100% of PBSC donors had recovered. Other factors associated with toxicity included obesity, increasing age, and female sex. In summary, this study provides extensive detail regarding individualized risk patterns of PBSC versus BM donation toxicity, suggesting donor profiles that can be targeted with interventions to minimize toxicity.

[Increasing participation of primary care in the management of people with human immunodeficiency virus: hospital care professionals express their views]. / Incremento de la participación de Atención Primaria en la asistencia al virus de la inmunodeficiencia humana: opinan los profesionales de las unidades hospitalarias.

AIM: To determine the opinions of infectious diseases professionals on the possibilities of monitoring patients with HIV in Primary Care. DESIGN: Qualitative study using in-depth interviews. LOCATION: Infectious Diseases Unit in the University Hospital "Virgen de la Victoria" in Málaga. PARTICIPANTS: Health professionals with more than one year experience working in infectious diseases. A total of 25 respondents: 5 doctors, 15 nurses and 5 nursing assistants. METHOD: Convenience sample. Semi-structured interviews were used that were later transcribed verbatim. Content analysis was performed according to the Taylor and Bogdan approach with computer support. Validation of information was made through additional analysis, expert participation, and feedback of part of the results to the participants. RESULTS: Hospital care professionals considered the disease-related complexity of HIV, treatment and social aspects that may have an effect on the organizational level of care. Professionals highlighted the benefits of specialized care, although opinions differed between doctors and nurses as regards follow up in Primary Care. Some concerns emerged about the level of training, confidentiality and workload in Primary Care, although they mentioned potential advantages related to accessibility of patients. CONCLUSIONS: Physicians perceive difficulties in following up HIV patients in Primary Care, even for those patients with a good control of their disease. Nurses and nursing assistants are more open to this possibility due to the proximity to home and health promotion in Primary Care.

Microplastics suspended in dust from different indoor environments in Barranquilla, Colombia: Predominant microparticles?

Considering that microplastics (MPs) are classified as ubiquitous pollutants, that air quality affects human health, and that people remain indoors most of the time, the need has arisen to evaluate the exposure to MPs within the suspended dust in indoor environments. With this objective, the present study carried out passive sampling to analyze the precipitation of microparticles in some indoor residential environments (2 apartments) and workplaces (an office, a pastry shop, a gift shop, and a paint shop) in Barranquilla, Colombia. The quantification and physical characterization of microparticles were carried out under a stereomicroscope, and the chemical characterization was carried out by infrared microspectroscopy (µFTIR). The highest average concentration of MPs in the apartments was found in the air-conditioned rooms (1.1 × 104 MP/m2/day), and concerning the workplaces, the gift shop and the paint shop were the spaces with a higher proportion of MPs (6.0-6.1 × 103 MP/m2/day), with polyesters being the main synthetic polymers, but being semi-synthetic particles the predominant among the samples. Regarding its morphology, fibers were the most abundant shape (>90%), grouping mainly in the 1000-5000 µm range, while the few fragments found were mostly grouped below 50 µm. Exposure by inhalation of MPs in adults was estimated between 1.7 × 102-1.6 × 103 MP/kg/day, while by ingestion it ranged between 2.7 × 102-2.4 × 103 MPs/kg/day. On the other hand, within our research, a significant presence of non-plastic microparticles was found, which reached up to 69% in analyzed samples, corresponding mainly to cotton and cellulose, so we suggest that these should also be included in future studies that aim to estimate potential health implications from exposure to suspended micropollutants.

Targeting with Structural Analogs of Natural Products the Purine Salvage Pathway in Leishmania (Leishmania) infantum by Computer-Aided Drug-Design Approaches.

Visceral Leishmaniasis (VL) has a high death rate, with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural analogs of natural products as potential novel drugs to treat VL. We selected structural analogs from natural products that have shown antileishmanial activities, and that may impede the purine salvage pathway using computer-aided drug-design (CADD) approaches. For these, we started with the vastly studied target in the pathway, the adenine phosphoribosyl transferase (APRT) protein, which alone is non-essential for the survival of the parasite. Keeping this in mind, we search for a substance that can bind to multiple targets throughout the pathway. Computational techniques were used to study the purine salvage pathway from Leishmania infantum, and molecular dynamic simulations were used to gather information on the interactions between ligands and proteins. Because of its low homology to human proteins and its essential role in the purine salvage pathway proteins network interaction, the findings further highlight the significance of adenylosuccinate lyase protein (ADL) as a therapeutic target. An analog of the alkaloid Skimmianine, N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide, demonstrated a good binding affinity to APRT and ADL targets, no expected toxicity, and potential for oral route administration. This study indicates that the compound may have antileishmanial activity, which was granted in vitro and in vivo experiments to settle this finding in the future.